PROSPECTIVE-STUDY OF BONE LOSS IN PREMENOPAUSAL AND POSTMENOPAUSAL WOMEN ON L-THYROXINE THERAPY FOR NONTOXIC GOITER

OBJECTIVE Hyperthyroidism is associated with increased bone turnover a nd bone resorption, but the effects of suppressive doses of thyroxine in treating non-toxic goitre remain unclear. We carried out a longitud inal study to evaluate the effect on bone of L-thyroxine (L-T4) therap y in women with non-toxic goitre. SUBJECTS Forty Caucasian women, 19 o f whom were pre-menopausal and 21 post-menopausal, were studied before and after 12 months' L-T4 therapy for non-toxic goitre; 40 women matc hed for age, body mass index and menopausal status were used as contro ls. DESIGN The minimal dosage of L-T4 (mean +/- standard error = 1.5 /- 0.1 mu g/kg(-1) day(-1)) was given to each patient to obtain subnor mal but detectable serum TSH (less than or equal to 0.2 mU/l). Patient s and controls were assessed for minor determinants of bone loss rate, such as genetic and behavioural factors. MEASUREMENTS Bone mineral de nsity (BMD) of the lumbar spine, femoral neck, trochanter and Ward's t riangle was measured by dual-energy X-ray absorptiometry at baseline a nd 12 months; serum and urine markers of bone turnover was measured at baseline, 3, 6 and 12 months. RESULTS No significant difference was d etected in BMD values between patients and controls either at presenta tion or at the 12-month follow-up. Pre-menopausal patients showed a si gnificant decrease in femoral neck BMD (-1.7 +/- 0.6%, P < 0.05) while controls showed no change + 0.2 +/- 0.9%, P = NS). Postmenopausal pat ients showed a significant decrease in BMD of the lumbar spine (-1.3 /- 0.6%, P < 0.05; controls + 0.0 +/- 0.4%, P = NS), femoral neck (-1. 5 +/- 0.6%, P < 0.05; controls -1.2 +/- 0.8%, P = NS) and trochanter ( -2.1 +/- 0.8%, P < 0.05; controls -1.4 +/- 0.9%, P = NS). In both pre- and post-menopausal patients the serum markers of bone turnover, alkal ine phosphatase and osteocalcin, showed an early and progressive incre ase. A linear relationship was found only between the 3-month values o f serum osteocalcin and the urine hydroxyproline/creatinine ratio in b oth pre-menopausal (r = 0.87, P < 0.01) and post-menopausal (r = 0.72, P < 0.05) patients. No correlation was found between bone loss or cha nges in bone turnover markers and L-T4 dose or thyroid hormone levels. CONCLUSION This longitudinal study suggests that TSH-suppressive ther apy with L-thyroxine for nontoxic goitre significantly increases the b one mineral turnover and might contribute to a BMD reduction, more mar ked on cortical bone, in both pre-and postmenopausal women.